DRUM Collection: Chemistry & Biochemistry Theses and Dissertationshttp://hdl.handle.net/1903/2752
Sun, 02 Aug 2015 07:11:06 GMT2015-08-02T07:11:06ZVisualizing Quantum Reactive Scattering Dynamicshttp://hdl.handle.net/1903/16699
Title: Visualizing Quantum Reactive Scattering Dynamics
Authors: Warehime, Michael
Abstract: The Born-Oppenheimer approximation, which allows a decoupling of electronic and nuclear motion, underlies the investigation of molecular dynamics. In some cases this decoupling is not possible, so that nuclear motion can induce changes in electronic state. It is then necessary to account for collision-induced transitions between multiple potential energy surfaces. This is an inherently quantum phenomena. In this dissertation we present a new way to visualize these non-adiabatic transitions in chemical reactions of open-shell atoms. Toward this end, we have developed new algorithms and developed a MATLAB-based software suite for simulating non-adiabatic reactions. We have also determined new molecular potential energy surfaces and their couplings required to simulate the reactive dynamics.Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/1903/166992015-01-01T00:00:00ZOn the Cyclopolymerization of 1,6-Heptadienes, and their Role as Poly(methylenecycloalkane)s in Stereoengineering and Block Copolymershttp://hdl.handle.net/1903/16672
Title: On the Cyclopolymerization of 1,6-Heptadienes, and their Role as Poly(methylenecycloalkane)s in Stereoengineering and Block Copolymers
Authors: Crawford, Kaitlyn
Abstract: The research presented herein, addresses key issues of homogeneous Group 4 single-site coordination polymerization (CP) catalysts for the production of polyolefins and polyolefin-like materials. Specifically, this research moves beyond the `one-catalyst one-material' paradigm to afford an array of amorphous polyolefin materials with high Tg from a single monomer. The multitude of microstructurally distinct materials available from a single starting olefin is attributed to stereoengineering: a technique, which reduces stereoblock length in a highly controlled fashion while retaining regioselectivity. The precatalysts employed in this work are previously reported Group 4 CS-symmetric or C1-symmetric pentamethylmonocyclopentadienyl amidinate complexes with the general formula {(&#951;5-C5R5)M[N(R1)C(R2)N(R3)]-(Me2)} (M = Zr, Hf, R = alkyl, Me = methyl), which are activated by cocatalysts such as N,N-dimethylanilinium tetrakis(pentafluorophenyl)-borate ([PhNMe2H][B(C6F5)4]). Living CP of 1,6-heptadiene and stereoengineering of the subsequent poly(methylenecycloalkane)s with the above complexes reveal a variety of stereochemically controlled, yet amorphous, poly(methylene-1,3-cyclohexane) (PMCH) materials with Tg values as high as 101 °C. Similar polymerization techniques have been applied, for the first time with Sita group complexes, towards the CP of the heteroatom-olefins such as diallyldimethylsilane (DAS). The controlled CP and stereoengineering of DAS resulted in amorphous poly(3,5-methylene-1,1-dimethyl-1-silacyclohexane) materials with Tg values as high as 127 °C. The living character and tunable stereoblock lengths of PMCH provided the opportunity to explore the high Tg polyolefin as the `hard' domain (A segment) in pure polyolefin AB block copolymers, BCPs. Specifically, amorphous AB diblock copolymers were synthesized using poly(1-hexene) as the `soft' B block to afford a series of microphase-separated morphologies without the deleterious effects of crystallization. Microphase-separated morphologies for were also observed for ABA triblock copolymers using atactic polypropylene as the `soft' segment (B block) and primary component. The latter BCPs were found to exhibit thermoplastic elastomeric properties. The work described in this document provides a foundation for the further expansion of the currently-limited pool of monomers to include heteroatom-olefins for CP with the aforementioned Group 4 transition metal complexes. Moreover, the formation of well-defined pure polyolefin block copolymers serve as an important contribution to the development of new polyolefin architectures.Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/1903/166722015-01-01T00:00:00ZBioorganic Chemistry of Prodigiosenes: Anion Transport, Basicity, Conformation and G-Quadruplex DNA Bindinghttp://hdl.handle.net/1903/16668
Title: Bioorganic Chemistry of Prodigiosenes: Anion Transport, Basicity, Conformation and G-Quadruplex DNA Binding
Authors: Rastogi, Soumya
Abstract: Naturally occurring prodigiosenes are produced by microorganisms such as Streptomyces and Serratia marcescens. Prodigiosenes are fascinating for their wide range of biological activities in the form of anti-cancer, immunosuppressive, and antimicrobial agents. Some of the analogs, such as prodigiosin, are currently undergoing preclinical and clinical trials. Despite such widespread interest, the origin of prodigiosin's biological activity has not been established unambiguously. Based on biological studies, it is known that prodigiosin plays a physiologically relevant role and has several cellular targets. The work described in this thesis explores some of the chemistry that may help explain prodigiosenes' biological activity.
A new series of analogs of prodigiosin bearing an additional methyl and a carbonyl group at the C-ring were evaluated as transmembrane anion transporters. The effect of C-ring modifications in these new prodigiosenes on their basicity, transmembrane anion transport ability and their in vitro anticancer activity was assessed. The ability of prodigiosenes to facilitate co-transport of H&#8314;Cl&#8315; leading to alteration of intracellular pH, and catalyze anion exchange across lipid bilayers has been proposed to be one of the cause of its anti-cancer activity. It has been suggested that the prodigiosenes bind anions in their protonated state at physiological pH. Prodigiosene analogs with modified B-ring demonstrated that the electronic nature of the substituent on the B-ring influences the basicity of these analogs, and consequently, their anion transport efficiency is also affected.
A study of the conformations of prodigiosin and its analogs was performed to learn about how the ligands orient in different solvents. This information could potentially link the preferred conformational states of these compounds and their observed biological activities. Lastly, we confirmed that prodigiosin binds at the 3&#712; end of a G-quadruplex DNA. The results from this chapter are significant as they widen the scope of developing prodigiosenes as G-quadruplex binding ligands or telomerase inhibiting agents. Further, they lead the way to revealing another possible mechanism to explain the anti-cancer activity of prodigiosenes.Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/1903/166682015-01-01T00:00:00ZThe Core of Eukaryotic Ribosomal Protein uS19 Functions as a Pivot Point Enhancing Eukaryotic Ribosome Flexibilityhttp://hdl.handle.net/1903/16608
Title: The Core of Eukaryotic Ribosomal Protein uS19 Functions as a Pivot Point Enhancing Eukaryotic Ribosome Flexibility
Authors: Bowen, Alicia Marie
Abstract: While most ribosomal elements are highly conserved in the three domains of life, over the course of evolution, significant differences have emerged as ribosomes have been subjected to different types of selective pressure. In prokaryotes and archaea, a single small subunit protein, uS13, partners with H38 (the A-site finger) and uL5 to form the B1a and B1b/c bridges, respectively. In eukaryotes, it appears that the small subunit component was split into two separate proteins during the course of evolution. One of these, also known as uS13 (previously known as S18), only participates in bridge B1b/c with uL5 in eukaryotes (previously known as L11). The other, called uS19 (previously known as S15) is the small subunit partner in the B1a bridge with H38. Here, poly-alanine mutants of the uS19/Us13 interface of uS19 were used to elucidate the evolutionary advantage of this split. A previously described chemical protection profile of the B7a bridge was utilized in order to determine the ribosomal rotational status of the selected mutants. rRNA structure probing analyses reveal that uS19/uS13 interface mutations shift the ribosomal rotational equilibrium toward the unrotated state. This perturbation of ribosomal rotational equilibrium also affected the ribosomes affinity for two intrinsic ligands: unrotated ribosomes exhibit increased affinity for ternary complex and disfavor binding of the translocase, eEF2. We posit that this mutation causes the normally flexible head region of the small subunit to "stiffen", thereby decreasing the ribosomes range of motion. A model is presented in which residues L112GH114 at the uS19/uS13 interface act as the ball in a "ball-and-socket joint", providing the increased flexibility required in the head region of the eukaryotic SSU as a consequence of the evolutionary process.Thu, 01 Jan 2015 00:00:00 GMThttp://hdl.handle.net/1903/166082015-01-01T00:00:00Z